Treatment of hemorrhagic lymphatic malformation of the tongue with a pulsed-dye laser

Hemorrhagic lymphatic malformation (formerly called hemolymphangioma) of the tongue is an uncommon malformation that may pose both functional and cosmetic problems for the patient. The challenge has been to find a conservative treatment with low morbidity and better results than those achieved with surgical excision, which has been the mainstay of therapy. We report a case of successful treatment of a hemorrhagic lymphatic malformation of the tongue with a variable-pulse 595-nm pulsed-dye laser (Vbeam; Candela Corp, Wayland, Mass). In this patient, pulsed-dye laser treatment of the hemorrhagic lymphatic malformation achieved satisfactory functional and cosmetic outcomes. Its use in superficial vascular lesions of the mucosa should be considered.     

Bacterial flora of leg ulcers in patients admitted to Department of Dermatology, Poznań University of Medical Sciences, during the 1998-2002 period

Venous leg ulcers are an important cause of morbidity in a significant percentage of the world population. The percentage of leg ulceration, either active or healed, in the European population is about 1%-2%. The aim of this study was to analyze the rate of colonization and qualitative composition of the bacterial flora isolated from leg ulcers in patients admitted to Dermatology Department, Poznań University of Medical Sciences, during the 1998-2002 period, with special reference to the infection risk factors. Bacteriological diagnosis of 175 wound swabs was performed in compliance with compulsory laboratory methods. In 173 positive results, the predominant culture composition included Staphylococcus aureus (56.57%), Pseudomonas aeruginosa (37.14%), Enterococcus faecalis (22.29%), Proteus mirabilis (13.71%) and Escherichia coli (12.57%). There was a significant increase in the incidence of Pseudomonas aeruginosa, Enterococcus faecalis and Escherichia coli, along with a decrease in the incidence of Staphylococcus aureus isolation during the study period. The rate of yeast-like fungi strains, mainly Candida albicans, recorded in culture composition showed a systematic increase. Changes in the qualitative and quantitative composition of bacterial flora, presence of multiple isolates, and concomitant diseases that may influence the characteristics of leg ulcer disease were closely monitored.     

A 60 kHz IntraLase femtosecond laser creates a smoother LASIK stromal bed surface compared to a Zyoptix XP mechanical microkeratome in human donor eyes

PURPOSE: To compare the stromal surfaces created by the latest mechanical microkeratome and femtosecond, laser technologies. METHODS: Laser in situ keratomileusis (LASIK) flaps were created in six fresh human globes unsuitable for transplantation. The eyes were placed in one of two groups of three globes each. One group had LASIK flaps created with a Zyoptix XP microkeratome using a 120-microm head and a fresh blade for each eye. Another group had flaps created at an attempted 100-microm thickness using the 60 kHz IntraLase femtosecond laser. Immediately following flap creation, the stromal beds were prepared for scanning electron microscopy (SEM). Qualitative roughness of the SEM images was graded by masked observers. Quantitative roughness of the SEM images was assessed using computerized software designed for roughness analysis. Mann-Whitney non-parametric statistical analysis was performed to compare groups. RESULTS: A statistically significant difference was noted in bed smoothness as measured by qualitative roughness and quantitative roughness scores. The IntraLase samples showed smoother stromal beds compared to the Zyoptix group (qualitative roughness = 2.0 +/- 0.7 pm vs 3.6 +/- 1.6 pm, P = .03; quantitative roughness = 20238 +/- 1869 pm vs 26368 +/- 8133 pm, P = .03). CONCLUSIONS: The 60 kHz IntraLase femtosecond laser and the Zyoptix XP 120-microm head using a new blade produced smooth, good quality, compact stromal beds qualitatively and quantitatively. Because the 60 kHz femtosecond laser permits a tight spot/line separation using low energy, it creates a smoother corneal stromal bed compared to previous femtosecond laser engines.     

Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity.

The anatomic response to intravitreal bevacizumab injection in three patients with aggressive, posterior retinopathy of prematurity is described. In all cases, the worse eye was treated with a single intravitreal injection of 0.75 mg of bevacizumab as monotherapy or complementary to laser therapy. In 24 hours, all injected eyes showed regression of the tunica vasculosa lentis and iris vessel engorgement and disappearance of iris rigidity. In addition, plus disease and retinal proliferation began to regress. None of the eyes required additional treatment. Follow-up of up to 10 months     

Corneal changes and wavefront analysis after orthokeratology fitting test

PURPOSE: To evaluate corneal changes and ocular aberrations during an orthokeratology test. DESIGN: A prospective, nonrandomized cohort study. METHODS: Fourteen myopic patients (26 eyes) underwent an orthokeratology fitting test with the BE contact lens (Ultravision Pty, Ltd, Brisbane, Australia). Best spectacle-corrected visual acuity (BSCVA), uncorrected (Ultravision Pty, Ltd, Brisbane, Australia) visual acuity (UCVA), subjective cycloplegic refraction, biomicroscopy, corneal topography, optical pachymetry, and aberrometry were performed at baseline and one and eight nights orthokeratology. The short-term effect of orthokeratology using corneal topography, tomography, and ocular aberrations was evaluated. RESULTS: The mean spherical equivalent changed from -2.24 +/- 0.98 diopters (D) at baseline to 0.15 +/- 0.76 D after the eight nights of lens wear (P = .001). All patients had an UCVA of 20/30, 69.2% with 20/20. Changes in central corneal pachymetry were not observed. There was a statistically significant increase in the temporal corneal thickness from night one, without any difference between nights one and eight (P > .001). A significant increase of higher-order root mean square values was observed from baseline (0.42 +/- 0.16 mum), night one (0.81 +/- 0.24 mum), and night eight (1.04 +/- 0.24 mum). Increases in coma (Z7+Z8) and spherical aberration (Z12) were observed. Positive horizontal (Z8) coma increased in right eyes, and negative horizontal (Z8) coma increased in left eyes (P < .001). CONCLUSIONS: Myopia reduction resulting from rapid central corneal flattening and improvement of UCVA occurred after orthokeratology. Higher-order aberrations (HOAs), particularly spherical aberration and coma, increased significantly during the orthokeratology test. An increase of temporal pachymetry and differences in coma direction induced between the eyes may be related to the subclinical lens decentration temporally.     

Transpupillary thermotherapy in exudative age-related macular degeneration

PURPOSE: Assessment of TTT results in patients with exudative age-related macular degeneration. MATERIAL AND METHODS: The study comprised of 65 patients (73 eyes), in age 50-84 years (average age-75 yrs). The diagnosis of exudative AMD was established on the basis of fundus examination and fluorescein angiography (FA) and in some cases on indocyanine green angiography. The baseline visual acuity (VA) ranged from counting fingers at 50 cm to 0.8. In 31 (42.5%) eyes occult CNV, in 11 (15%) minimally classic CNV and in 31 (42.5%) eyes predominantly classic CNV were observed. Subfoveal CNV was present in 70 (95.9%) eyes and perifoveal in 3 (4.1%). TTT was delivered using a diode laser at 810 nm wavelength, a spot size of 1.2 to 4.5 mm and a duration of 60 seconds for each spot with power settings between 320-800 mW. Follow-up examinations were carried out every 10-12 weeks. In cases with persistent leakage from CNV in late frames of FA a retreatment was performed. The follow-up period ranged from 6 to 28 months (average - 9.8 months). RESULTS: Visual acuity improved in 22 (30.1%) eyes, stabilized in 34 (46.6%) and deteriorated in 17 (23.3%). Fluorescein angiography showed no CNV leakage in 58 (79.5%) eyes. In 56 (71.8%) with regression of leakage in fluorescein angiography improvement or stabilization of visual acuity was detected. Subretinal haemorrhages after TTT were observed in 4 eyes (5.5%). At the end of the follow-up period fibrosis of CNV was detected in 12 eyes (16.4%). CONCLUSIONS: TTT is effective and safe method of treatment of occult and classic CNV in a course of wet AMD. In a majority of cases TTT results in total or partial regression of CNV and stabilization of visual acuity.     

Brazilian guidelines proposal for screening and treatment of retinopathy of prematurity (ROP)

Retinopathy of prematurity is one of the main causes of childhood blindness. Worldwide, there are more than 50,000 children blind due to retinopathy of prematurity. Visual impairment is a consequence of retinal detachment. It can be detected by serial ophthalmologic examination of infants at risk, and those identified with the severe form of the disease can be treated by laser or cryotherapy, which can decrease significantly the blindness due to ROP. The Brazilian Society of Pediatrics, Brazilian Council of Ophthalmology and Brazilian Society of Pediatric Ophthalmology suggest a guideline for the detection and treatment of retinopathy of prematurity in Brazil. This document was based on the results of the I Workshop of Retinopathy of Prematurity and presents the attributes for the implementation of an efficient diagnostic and treatment program.     

The role of hyperthermic perfusion as a first step in the treatment of soft tissue sarcoma of the extremities

Eighty-six patients with locally advanced, high-grade soft tissue sarcomas of the extremities were studied prospectively in order to determine the efficacy of hyperthermic perfusion (HP) or hyperthermic antiblastic perfusion (HAP) as the first step of a combined multimodality therapy. The immediate response was evaluated in terms of tumor regression, and results confirmed the in vivo sensitivity of human sarcomas to the selective antineoplastic action of heat alone or combined with drugs (melphalan, actinomycin D, and cis-platinum). HAP has been shown to be simpler and safer than HP, and it is now currently routinely employed. As far as the long-term cure is concerned, all the patients have been evaluated for functional results, locoregional control, and survival, according to the different treatment schedules. The first clinical trials employed HP or HAP followed by delayed surgery alone. In 11 of 17 evaluable patients treated with HP, and in 17 of 29 treated with HAP, conservative surgery could be performed. A high incidence of locoregional relapse (24%) occurred, with low overall survival rates: 50.1% and 31.7% at 5 and 10 years after HP plus surgery, and 47.9% after HAP plus surgery at both 5 and 10 years. The protocol was, therefore, modified to include continuous intraarterial infusion of Adriamycin® (ADR) (17 patients) or radiotherapy (9 patients) before surgery. The results obtained thus far may be summarized as follows: (a) conservative surgery with functional limb-salvage was possible in all patients; (b) the percentage of locoregional failure decreased to approximately 12% after HAP + ADR infusion + excision, the 5- and 10-year overall survival rates both being 77.6 %, and the 5- and 10-year disease-free rates both being 57.8%; (c) no local recurrences occurred in the group treated with HAP + radiotherapy + excision with a 5-year overall survival rate of 71.5% and a 5-year disease-free rate of 50.4%. In conclusion, the combined multimodality approaches employed appear to have improved both functional results and long-term cure, even though these must be further confirmed on a larger series of patients.

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Resumen Ochenta y seis pacientes con sarcomas de los tejidos blandos de las extremidades, de alto grado histológico, e invasión local avanzada fueron estudiados en forma prospectiva con el objeto de determinar la eficacia de la perfusión hipertérmica (PH) o la perfusión hipertérmica antiblástica (PHA) como primer paso dentro de una terapia combinada multimodal.La respuesta inmediata fue valorada en términos de la regresión tumoral, y los resultados confirmaron la sensibilidad in vivo de los sarcomas humanos a la acción antineoplásica selectiva del calor sólo o combinado con drogas (melfalán, actinomicina D, y cis-platino). La PHA ha demostrado ser más sencilla y más segura que la PH y actualmente es utilizada en forma rutinaria.En lo referente a curación a largo plazo, todos los pacientes han sido evaluados en cuanto a resultados funcionales, control locorregional, y supervivencia, de acuerdo a los diferentes programas terapéuticos.En los primeros ensayos clínicos se utilizó PH o PHA seguida de cirugía solamente. En 11 de 17 pacientes valorables tratados con PH y 17 con PHA, fue posible realizar cirugía conservadora. Se presentó una incidencia alta de relapso locorregional (24%), con tasas bajas de supervivencia global: 50.1% y 31.7% a 5 y 10 años con PH y cirugía, y 47.9% con PHA y cirugía tanto a 5 como a 10 años.El protocolo fue consecuentemente modificado para incluir una infusión intraarterial continua de Adriamicina® (ADR) (17 pacientes) o radioterapia (9 pacientes) antes de la cirugía.Los resultados logrados hasta el momento pueden ser resumidos así: (a) la cirugía conservadora con salvamento del miembro fue posible en la totalidad de los pacientes; (b) el porcentaje de falla locorregional disminuyó aproximadamente 12% después de PHA + infusión de ADR + resección, con supervivencias globales a 5 y 10 años de 77.6%, y tasas de estado libre de enfermedad a 5 y 10 años de 57.8%; (c) no se presentaron recurrencias locales en el grupo tratado con PHA + radioterapia + resección, con una tasa de supervivencia global a 5 años de 71.5% y una tasa de estado libre de enfermedad a 5 años de 50.4%.En conclusión, los aproches con terapia combinada multimodal empleados parecen haber mejorado tanto los resultados funcionales como las tasas de curación a largo plazo, aunque estos resultados aún deben ser reconfirmados en una serie mayor de pacientes.

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Résumé Une étude prospective concernant 86 malades qui présentaient un sarcome des parties molles des membres de stade évolutif avancé a été entreprise pour déterminer l'efficacité de la perfusion hyperthermique ou de la perfusion hyperthermique antiblastique en tant que première étape d'un traitement à modalités multiples.La réponse immédiate a été appréciée en fonction de la régression tumorale. Les résultats ont confirmé la sensibilité in vivo des sarcomes humains à l'action antinéoplasique sélective de la chaleur employée isolemment ou combinée avec des drogues (melphalan, actinomycine D, et cis-platinum). La perfusion hyperthermique antiblastique s'est montrée plus simple et plus sûre que la perfusion hyperthermique, et de ce fait est devenue une méthode thérapeutique normalement employée.Pour apprécier l'action thérapeutique à long terme tous les malades ont été étudiés en tenant compte des résultats fonctionnels, du contrôle loco-régional, et de la survie obtenus selon les différentes thérapeutiques appliquées.Les premiers essais ont eu recours à l'hyperthermie thermique ou à l'hyperthermie thermique antiblastique suivie d'une intervention chirurgicale. Chez 11 des 17 malades traités par l'hyperthermie thermique, et chez 17 des 29 malades soumis à l'hyperthermie antiblastique le traitement chirurgical conservateur a pu être réalisé. Les résultats furent les suivants: fréquence importante des récidives loco-régionales (24%); taux global de survie bas: 50.1% et 31.7% à 5 ans et 10 ans après perfusion hyperthermique suivie de chirurgie, ce taux étant de 47.9% après perfusion hyperthermique antiblastique suivie de chirurgie à 5 ans et 10 ans.En fonction de ces résultats le protocole thérapeutique fut modifié en y ajoutant une transfusion intra-artérielle continue d'Adriamycine® (17 malades) ou de la radiothérapie (9 malades) avant l'intervention.Les résultats obtenus à ce jour peuvent se résumer ainsi: (a) la chirurgie conservatrice permettant de sauver un membre fonctionnel est toujours possible; (b) la poucentage d'échec régional décroit environ jusqu' à 12% après perfusion hyperthermique antiblastique associée à la perfusion d'Adriamycine® et l'excision, le taux global de survie à 5 ans et 10 ans étant de 77.6%, le taux d'absence de la maladie à 5 ans et 10 ans étant de 57.8%; (c) aucune récidive locale n'est survenue dans le groupe traité par perfusion hyperthermique antiblastique associé à la radiothérapie et à l'exérèse, le taux global de survie à 5 ans étant de 71.5% et le taux d'absence de la maladie à 5 ans étant de 50.4%.En conclusion le traitement qui a été employé associant plusieurs modalités thérapeutiques a entrainé une amélioration des résultats fonctionnels et de la cure à long terme encore que ce fait demande a été confirmé par une étude étendue à un plus grand mombre de malades.

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Supported by Special Project Hyperthermia from the Italian Ministry of Health.     

Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection

Because CD4+ T cells play a key role in aiding cellular immune responses, we wanted to assess whether increasing numbers of gene-engineered antigen-restricted CD4+ T cells could enhance an antitumor response mediated by similarly gene-engineered CD8+ T cells. In this study, we have used retroviral transduction to generate erbB2-reactive mouse T-cell populations composed of various proportions of CD4+ and CD8+ cells and then determined the antitumor reactivity of these mixtures. Gene-modified CD4+ and CD8+ T cells were shown to specifically secrete Tc1 (T cytotoxic-1) or Tc2 cytokines, proliferate, and lyse erbB2+ tumor targets following antigen ligation in vitro. In adoptive transfer experiments using severe combined immunodeficient (scid) mice, we demonstrated that injection of equivalent numbers of antigen-specific engineered CD8+ and CD4+ T cells led to significant improvement in survival of mice bearing established lung metastases compared with transfer of unfractionated (largely CD8+) engineered T cells. Transferred CD4+ T cells had to be antigen-specific (not just activated) and secrete interferon gamma (IFN-gamma) to potentiate the antitumor effect. Importantly, antitumor responses in these mice correlated with localization and persistence of gene-engineered T cells at the tumor site. Strikingly, mice that survived primary tumor challenge could reject a subsequent rechallenge. Overall, this study has highlighted the therapeutic potential of using combined transfer of antigen-specific gene-modified CD8+ and CD4+ T cells to significantly enhance T-cell adoptive transfer strategies for cancer therapy.